CN103989647A - Tenoxicam dispersible tablet and preparation method thereof - Google Patents
Tenoxicam dispersible tablet and preparation method thereof Download PDFInfo
- Publication number
- CN103989647A CN103989647A CN201410239716.7A CN201410239716A CN103989647A CN 103989647 A CN103989647 A CN 103989647A CN 201410239716 A CN201410239716 A CN 201410239716A CN 103989647 A CN103989647 A CN 103989647A
- Authority
- CN
- China
- Prior art keywords
- tenoxicam
- acid
- dispersible tablet
- starch
- sodium
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 229960002871 tenoxicam Drugs 0.000 title claims abstract description 85
- 239000007919 dispersible tablet Substances 0.000 title claims abstract description 69
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- WZWYJBNHTWCXIM-UHFFFAOYSA-N tenoxicam Chemical compound O=C1C=2SC=CC=2S(=O)(=O)N(C)C1=C(O)NC1=CC=CC=N1 WZWYJBNHTWCXIM-UHFFFAOYSA-N 0.000 title claims abstract 23
- 239000011230 binding agent Substances 0.000 claims abstract description 11
- 239000000945 filler Substances 0.000 claims abstract description 11
- 239000003826 tablet Substances 0.000 claims abstract description 11
- 239000000314 lubricant Substances 0.000 claims abstract description 10
- 239000007884 disintegrant Substances 0.000 claims abstract 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 47
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 45
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 34
- 239000000203 mixture Substances 0.000 claims description 25
- 239000000243 solution Substances 0.000 claims description 25
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- 229920002472 Starch Polymers 0.000 claims description 19
- 239000008107 starch Substances 0.000 claims description 19
- 235000019698 starch Nutrition 0.000 claims description 19
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 18
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 18
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 18
- 239000011734 sodium Substances 0.000 claims description 18
- 229910052708 sodium Inorganic materials 0.000 claims description 18
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 17
- 235000019359 magnesium stearate Nutrition 0.000 claims description 17
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- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 15
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 15
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- 239000008101 lactose Substances 0.000 claims description 15
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- 239000002253 acid Substances 0.000 claims description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 13
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- 239000008187 granular material Substances 0.000 claims description 13
- 239000007779 soft material Substances 0.000 claims description 10
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 8
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 7
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- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 7
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 6
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- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 4
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- 235000011054 acetic acid Nutrition 0.000 claims description 4
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- 239000001630 malic acid Substances 0.000 claims description 4
- 235000011090 malic acid Nutrition 0.000 claims description 4
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- QAIPRVGONGVQAS-DUXPYHPUSA-N trans-caffeic acid Chemical compound OC(=O)\C=C\C1=CC=C(O)C(O)=C1 QAIPRVGONGVQAS-DUXPYHPUSA-N 0.000 claims description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 3
- 108010010803 Gelatin Proteins 0.000 claims description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- 229920000881 Modified starch Polymers 0.000 claims description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 3
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- 235000019322 gelatine Nutrition 0.000 claims description 3
- 235000011852 gelatine desserts Nutrition 0.000 claims description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 3
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- 239000000594 mannitol Substances 0.000 claims description 3
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- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 3
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- ACEAELOMUCBPJP-UHFFFAOYSA-N (E)-3,4,5-trihydroxycinnamic acid Natural products OC(=O)C=CC1=CC(O)=C(O)C(O)=C1 ACEAELOMUCBPJP-UHFFFAOYSA-N 0.000 claims description 2
- 239000004375 Dextrin Substances 0.000 claims description 2
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- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
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- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
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- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 125000005211 alkyl trimethyl ammonium group Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
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- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
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- 229940111133 antiinflammatory and antirheumatic drug oxicams Drugs 0.000 description 1
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- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
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- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000013681 dietary sucrose Nutrition 0.000 description 1
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
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- 201000010099 disease Diseases 0.000 description 1
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- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
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- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
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- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Chemical class CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 150000002333 glycines Chemical class 0.000 description 1
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical class COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
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- 229940067606 lecithin Drugs 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
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- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
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- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 229960000540 polacrilin potassium Drugs 0.000 description 1
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- 229920000058 polyacrylate Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 description 1
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- 239000004302 potassium sorbate Substances 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- WVWZXTJUCNEUAE-UHFFFAOYSA-M potassium;1,2-bis(ethenyl)benzene;2-methylprop-2-enoate Chemical compound [K+].CC(=C)C([O-])=O.C=CC1=CC=CC=C1C=C WVWZXTJUCNEUAE-UHFFFAOYSA-M 0.000 description 1
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- PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 description 1
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Landscapes
- Medicinal Preparation (AREA)
Abstract
本发明公开了一种替诺昔康分散片及其制备方法和应用。本发明所述的替诺昔康分散片由如下按照重量百分数计的组分组成：替诺昔康2～20％，填充剂10～50％，崩解剂10～50％，酸化剂10～60％，粘合剂0.1～20％，润滑剂及助流剂0.1～30％。本发明所述分散片与普通片比较，本发明所述的替诺昔康分散片中不含表面活性剂，其溶解性、分散性和崩解性亦良好，可在1分钟内即可崩解完全。采用本发明方法制备的替诺昔康分散片，溶出度高，生物利用度好，体内分布迅速，质量稳定，口感好，其制备方法简单易行，适用于工业生产。The invention discloses a tenoxicam dispersible tablet, a preparation method and application thereof. The tenoxicam dispersible tablet of the present invention is composed of the following components by weight percentage: 2-20% of tenoxicam, 10-50% of filler, 10-50% of disintegrant, 10-50% of acidulant 60%, binder 0.1-20%, lubricant and glidant 0.1-30%. Compared with the common tablet, the dispersible tablet of the present invention does not contain surfactant, and its solubility, dispersibility and disintegration are also good, and it can be disintegrated within 1 minute. solution completely. The tenoxicam dispersible tablet prepared by the method of the invention has high dissolution rate, good bioavailability, rapid distribution in the body, stable quality and good taste, and the preparation method is simple and easy, and is suitable for industrial production.
Description
Invention field
The present invention relates to chemical pharmacy field, be specifically related to a kind of tenoxicam dispersible tablet and preparation method thereof.
Background of invention
Arthritis is a kind of commonly encountered diseases, chronic disease, wherein taking osteoarthritis and rheumatoid arthritis as principal mode.It is reported, China approximately has 18% people to suffer from the arthritis of certain form, and number of the infected exceedes 200,000,000.The mankind's health in arthritis serious threat, has influence on patient's live and work, some patient be can't take care of oneself, disability.Some patient's activity is restricted, arthroncus, stiff and pain, and severe patient joint permanent deformation, is the major reason that old people is disabled, and therefore needs timely treatment.
Tenoxicam (Tenoxicam), CA accession number 59804-37-4, chemistry 4_ hydroxyl _ 2_ methyl-N-(2-pyridine radicals)-2H-thieno [2 by name, 3-e]-l, 2-thiazine-3-Methanamide _ 1, 1_ dioxide roxy-2-methyl-N-2-pyridinyl-2H-thieno[2, 3_e]-1, 2-thiazine-3_carboxam ide1, 1-dioxide), yellow crystal powder, belong to NSAID (non-steroidal anti-inflammatory drug) former times health (Oxicams) class medicine, can suppress cyclooxygenase (COX) and block arachidonic metabolism, thereby the generation of blocking-up prostaglandin, to reach antiinflammatory, analgesic activity.This medicine oral absorption is rapid, and consumption is few, and after administration, 30 minutes pain disappears, and lasting medicine, and the half-life reaches 70 hours.Metabolism is complete in vivo, is hydrophilic, and thoroughly to skin, therefore dermoreaction is slight hardly.Can penetrate synovial fluid, synovial fluid Chinese medicine concentration is about 40% of blood drug level.Clinical treatment rheumatism, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and stndon sheath moxibustion, bursitis, various headache, sciatica, backache and the gouty arthritises etc. of being used for the treatment of, aspect rheumatic arthritis, osteoarthritis treatment, effect is particularly remarkable.
Existing market sell is tenoxicam conventional tablet, there is not yet dispersible tablet pertinent literature report, and unexposed drug component ratio of the present invention, do not adopt acidulant yet, tenoxicam dispersible tablet provided by the invention adopts acidulant by its parcel or wraps up mutually, thereby the effect that reaches embedding, disintegration rate is fast, has also improved its bioavailability simultaneously.
Summary of the invention
The invention provides a kind of tenoxicam dispersible tablet, is according to existing tenoxicam pharmaceutical dosage forms or adding surfactant has the problems such as stimulation and bioavailability are not high to body, or does not adopt acidulant.The invention provides a kind of tenoxicam dispersible tablet, adopt acidulant by its parcel or parcel mutually, thereby reach the effect of embedding, and through repetition test by each component screening to weight ratio of the present invention,
Be surprised to find that the dispersible tablet steady quality obtaining, stripping is fast, in body, distributes rapidly, and bioavailability is high,
Dispersibility, disintegrative are good, can disintegrate in 1 minute complete, and this product is containing surfactant, and can reduce stimulates body.
On the one hand, the invention provides a kind of tenoxicam dispersible tablet, it comprises as follows according to the component of percetage by weight meter: tenoxicam 0.2～20%, filler 10～50%, disintegrating agent 10～50%, acidulant 10～60%, binding agent 0.1～20%, lubricant and fluidizer 0.1～30%.
Some embodiments therein, tenoxicam dispersible tablet of the present invention, it comprises as follows according to the component of percetage by weight meter: tenoxicam 2%, filler 40%, disintegrating agent 43%, acidulant 10%, binding agent 2%, lubricant and fluidizer 3%.
In other embodiments, tenoxicam dispersible tablet of the present invention, it comprises the component by following percetage by weight:
Tenoxicam 20g
Lactose 300g
Crospolyvinylpyrrolidone 90g
Carboxymethylstach sodium 200g
Hydroxypropyl methylcellulose 3.5g
Citric acid 100g
Micropowder silica gel 25g
Magnesium stearate 7.5g
Water 175
95% ethanol 114g
Make 1000.
In other embodiments, tenoxicam dispersible tablet of the present invention, it comprises the component by following percetage by weight:
Tenoxicam 10g
Lactose 300g
Crospolyvinylpyrrolidone 100g
Carboxymethylstach sodium 200g
Hydroxypropyl methylcellulose 3.5g
Citric acid 100g
Micropowder silica gel 25g
Magnesium stearate 7.5g
Water 175
95% ethanol 114g
Make 1000.
Some embodiments therein, tenoxicam dispersible tablet of the present invention, wherein, described filler is a kind of in starch, Icing Sugar, dextrin, lactose, microcrystalline Cellulose, mannitol, sorbitol or xylitol or their mixture.
Some embodiments therein, tenoxicam dispersible tablet of the present invention, wherein, described disintegrating agent is a kind of in microcrystalline Cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross-linked carboxymethyl cellulose sodium, crospolyvinylpyrrolidone, crosslinked carboxymethyl fecula sodium, dried starch or their mixture.
Some embodiments therein, tenoxicam dispersible tablet of the present invention, wherein, described acidulant is a kind of in citric acid, lactic acid, acetic acid, ethanedioic acid, malonic acid, succinic acid, tartaric acid, adipic acid, malic acid, nicotinic acid, pectic acid, ascorbic acid, caffeic acid, fumaric acid, maleic acid, phosphoric acid solution or their mixture.
Some embodiments therein, tenoxicam dispersible tablet of the present invention, wherein, described binding agent is a kind of in hypromellose, sodium carboxymethyl cellulose, starch, pregelatinized Starch, polyvidone, gelatin, Polyethylene Glycol, ethanol, water or their mixture.
Some embodiments therein, tenoxicam dispersible tablet of the present invention, wherein, described lubricant and fluidizer are a kind of of micropowder silica gel, magnesium stearate, silicon dioxide, Pulvis Talci, Polyethylene Glycol apoplexy due to endogenous wind or their mixture.
On the other hand, the present invention relates to a kind of preparation method of tenoxicam dispersible tablet, it comprises the steps: that (1) sieve tenoxicam and pharmaceutic adjuvant respectively; Binding agent be dissolved in concentration be 85% or following alcoholic solution or aqueous solution in after, then the acidulant of recipe quantity is dissolved in the solution containing binding agent, obtain acid solution; (2) tenoxicam is mixed homogeneously with filler, disintegrating agent, fluidizer after adopting the made acid solution embedding of step (1), adds binding agent, mixes, and makes soft material; (3) soft material is crossed to 14～30 mesh sieves, 40～60 DEG C dry, 14～30 order granulate; (4) add lubricant, mix homogeneously; (5) tabletting, makes tenoxicam dispersible tablet.
Some embodiments therein, the preparation method of tenoxicam dispersible tablet of the present invention wherein, is that tenoxicam and acid solution are passed through to fluid bed embedding with acid solution embedding described in step (2), or tenoxicam is put into together with acid solution to colloid mill and sheared, drier.
The prescription ratio of tenoxicam dispersible tablet of the present invention is not by teaching material or other reference material gained, but by the testing program gained conforming with the regulations in a large number, made dispersible tablet has carried out quality research, meets " Chinese Pharmacopoeia " 2010 editions two and make by oneself about dispersible tablet and other requirement of quality standard.In research, find the obvious existing conventional tablet of dissolution of technical solution of the present invention.
Compared with prior art, the present invention has following beneficial effect:
(1) tenoxicam is made tablet formulation by the present invention, and each drug component ratio is to be screened and obtained by repetition test, can significantly improve its bioavailability;
(2) the present invention granulates after adopting acidulant to process in the preparation of tenoxicam dispersible tablet, greatly improves its bioavailability;
(3) tablet formulation that the present invention makes, compared with ordinary tablet, stripping is rapid, and disintegrative is good, and disintegrate completely in 1 minute absorbs soon, and bioavailability is high, stable in properties;
(4) tablet formulation that the present invention makes, does not use surface active agent solubilization in manufacturing process, reduce body is stimulated, and has reduced the untoward reaction of medicine, has increased patient's compliance.
Excipient of the present invention comprises, but be not limited to, ion-exchanger, aluminum, aluminium stearate, lecithin, serum albumin, as human albumin, buffer substance is as phosphate, glycine, sorbic acid, potassium sorbate, the partial glycerol ester admixture of saturated vegetable fatty acid, water, salt or electrolyte, as protamine sulfate, sodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salt, colloid silicon, magnesium trisilicate, polyvinylpyrrolidone, polyacrylate, wax, polyethylene-polyoxypropylene-blocking-up polymer, lanoline, sugar, as lactose, dextrose plus saccharose, starch is as corn starch and potato starch, the derivant of cellulose and it is as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate, natural gum powder, Fructus Hordei Germinatus, gelatin, Pulvis Talci, adjuvant is as cocoa butter and suppository wax, oily as Oleum Arachidis hypogaeae semen, Oleum Gossypii semen, safflower oil, Oleum Sesami, olive oil, Semen Maydis oil and Oleum Glycines, glycols compound, as propylene glycol and Polyethylene Glycol, esters is as ethyl oleate and ethyl laurate, agar, buffer agent is as magnesium hydroxide and aluminium hydroxide, alginic acid, pyrogen-free water, Deng oozing salt, Lin Ge (family name) solution, ethanol, phosphate buffer solution, and other nontoxic proper lubrication agent are as sodium laurylsulfate and magnesium stearate, coloring agent, releasing agent, coating dress material, sweeting agent, flavoring agent and spice, antiseptic and antioxidant.
Pharmaceutical composition of the present invention can also optionally contain one or more diluent.The example of diluent comprises mannitol, sorbitol, biphosphate calcium dihydrate, microcrystalline Cellulose and efflorescence cellulose.Preferred diluent is microcrystalline Cellulose.Microcrystalline Cellulose can be obtained from several suppliers, comprises Avicel PH101, Avicel PH102, Avicel PH103, Avicel PH105 and Avicel PH200 that FMCCorporation manufactures.
Pharmaceutical composition of the present invention can also optionally contain disintegrating agent.Disintegrating agent can be the one in several modified starches, modified cellulose polymer or polycarboxylic acids, such as crosslinked Carboxymethyl cellulose sodium, Explotab, polacrilin potassium and calcium carboxymethylcellulose (CMCCalcium).In one embodiment, disintegrating agent is croscarmellose sodium.Croscarmellose sodium NF type A obtains with trade name " Ac-di-sol " on market.
Pharmaceutical composition of the present invention can also optionally contain one or more surfactants or wetting agent.Surfactant can be anion, cation or neutral surface active agent.Anion surfactant comprises sodium lauryl sulfate, dodecyl sodium sulfate, oleyl sodium sulfate and the sodium laurate mixing with stearate and Talcum.Cationic surfactant comprises benzalkonium chloride and alkyl trimethyl ammonium bromide.Neutral surface active agent comprises glycerol list olein, polyoxyethylene sorbitan fatty acid ester, polyvinyl alcohol and anhydro sorbitol fat.The embodiment of wetting agent comprises poloxamer, polyoxyethylene alkyl ether, castor oil derivatives and polyoxyethylene 8 stearate fat.
The present invention can also optionally join antioxidant in preparation, thereby gives its chemical stability.Antioxidant is selected from the extract of a-tocopherol, Y-tocopherol, S-tocopherol, tocopherol enrichment natural origin, sodium or calcium salt, the Vitamin C acyl cetylate of L-AA and it, amass wealth by heavy taxation propyl propionate, amass wealth by heavy taxation misery ester, amass wealth by heavy taxation sour dodecyl ester, Yoshinox BHT (BHT) and butylated hydroxyanisol (BHA).In one embodiment, antioxidant is BHT or BHA.
The preferred dosage form of drug composition of the present invention is the tablet of preparing by compression method.Described tablet can carry out film with the mixture such as hydroxypropyl cellulose and hydroxypropyl emthylcellulose, contains titanium dioxide and/or other coloring agent, such as ferrum oxide, dyestuff and Se Dian in this mixture; The mixture of polyvinyl alcohol (PVA) and Polyethylene Glycol (PEG), contains titanium dioxide and/or other coloring agent, such as ferrum oxide, dyestuff and Se Dian; Or any other suitable instant-free coating agent.Coating provides taste masked and other stability to final tablet.What commercially available film provided for Colorcon is preparation mixture of powders
.
The present invention can also add sweeting agent and/or fumet.
Detailed description of the invention
Further explain the present invention below in conjunction with embodiment, but embodiment does not limit in any form to the present invention.
Embodiment 1
Tenoxicam 20g
Lactose 300g
Crospolyvinylpyrrolidone 200g
Carboxymethylstach sodium 200g
Hydroxypropyl methylcellulose 7g
Micropowder silica gel 30g
Magnesium stearate 15g
Water 153g
95% ethanol 100g
Make 1000.
Preparation method:
Step 1: the tenoxicam of having pulverized and pharmaceutic adjuvant are crossed respectively to 120 mesh sieves, and hydroxypropyl methylcellulose first uses hot water swelling, is stirred to dissolving, then adds ethanol, makes concentration of alcohol reach 80%.
Step 2: press recipe quantity by tenoxicam, lactose, polyvinylpolypyrrolidone, micropowder silica gel mix homogeneously, add the solution of hypromellose described in step 1 to make soft material.
Step 3: made soft material in step 2 is crossed to 18 mesh sieves and granulate, 50 DEG C dry, and moisture is 2.6%, 18 mesh sieve granulate.
Step 4: mix homogeneously with magnesium stearate making granule in step 3.
Step 5: semi-finished product detect, and determine sheet weight, and tabletting, obtains tenoxicam dispersible tablet.
Embodiment 1 dispersible tablet smooth in appearance, dispersibility meets relevant regulations, but dissolution is not good.
Embodiment 2
Tenoxicam 20g
Lactose 300g
Crospolyvinylpyrrolidone 90g
Carboxymethylstach sodium 200g
Hydroxypropyl methylcellulose 3.5g
Citric acid 100g
Micropowder silica gel 25g
Magnesium stearate 7.5g
Water 175
95% ethanol 114g
Make 1000.
Preparation method:
Step 1: the tenoxicam of having pulverized and pharmaceutic adjuvant are crossed respectively to 120 mesh sieves, and hydroxypropyl methylcellulose first uses hot water swelling, is stirred to dissolving, then adds ethanol, makes concentration of alcohol reach 80%.Separately get above-mentioned hydroxypropyl methylcellulose solution 3.5g, add 175g water, add citric acid mix homogeneously.
Step 2: recipe quantity tenoxicam is mixed homogeneously with recipe quantity lactose, crospolyvinylpyrrolidone, carboxymethylstach sodium, micropowder silica gel after the embedding of fluid bed acid solution with citric acid solution in step 1, adds described in step 1, to remain hypromellose solution and make soft material.
Step 3: made soft material in step 2 is crossed to 16 mesh sieves and granulate, 50 DEG C dry, and moisture is 2.5%, 16 mesh sieve granulate.
Step 4: mix homogeneously with magnesium stearate making granule in step 3.
Step 5: semi-finished product detect, and determine sheet weight, and tabletting, obtains tenoxicam dispersible tablet.
Embodiment 2 has added acidulant, has reduced the amount of disintegrating agent, and technique is optimized on the basis of embodiment 1, after first acidification, granulates again, finds dispersible tablet smooth in appearance, and dissolution is better, and dispersion effect is good, substantially again can disintegrate in 1 minute complete.
Embodiment 3
Tenoxicam 20g
Crospolyvinylpyrrolidone 350g
Carboxymethylstach sodium 250g
Hydroxypropyl methylcellulose 3.5g
Citric acid 100g
Micropowder silica gel 15g
Magnesium stearate 7.5g
Water 189
95% ethanol 100g
Make 1000.
Preparation method is with embodiment 2.
Implementing 3 increases crospolyvinylpyrrolidone, carboxymethylstarch sodium content, and dispersible tablet dispersibility meets 2010 editions pharmacopeia requirements, and dissolution is better.
Embodiment 4
It is identical that embodiment 4 and embodiment 3 write out a prescription, and selects different acidify embedding modes, and tenoxicam and acidulant solution are put into colloid mill and sheared, then spraying is dry.The indices of dispersible tablet and the embodiment 3 made dispersible tablet there was no significant difference of writing out a prescription.
Embodiment 5
Tenoxicam 20g
Lactose 300g
Crospolyvinylpyrrolidone 150g
Carboxymethylstach sodium 100g
Starch 3.5g
Citric acid 100g
Acetic acid 100g
Micropowder silica gel 15g
Magnesium stearate 7.5g
Water 229g
Make 1000.
Preparation method:
Step 1: the tenoxicam of having pulverized and pharmaceutic adjuvant are crossed respectively to 120 mesh sieves, and starch adds water and makes starch slurry.Get the starch slurry 50g preparing, stir and add 180g water, then add citric acid, mix equal Uniform.Step 2: recipe quantity tenoxicam is mixed homogeneously with recipe quantity lactose, crospolyvinylpyrrolidone, carboxymethylstach sodium, micropowder silica gel, acetic acid after the embedding of fluid bed acid solution with part acid solution in step 1, adds remaining starch slurry described in step 1 to make soft material.
Step 3: made soft material in step 2 is crossed to 24 mesh sieves and granulate, 60 DEG C dry, and moisture is 2.4%, 24 mesh sieve granulate.
Step 4: mix homogeneously with magnesium stearate making granule in step 3.
Step 5: semi-finished product detect, and determine sheet weight, and tabletting, obtains tenoxicam dispersible tablet.
Embodiment 5 starch in replace hydroxypropyl methylcellulose, all the other are constant, find that made dispersible tablet hardness declines to some extent at equal pressure condition lower sheeting, but also meet 2010 editions pharmacopeia dispersible tablet standards.
Embodiment 6
Tenoxicam 20g
Starch 300g
Crospolyvinylpyrrolidone 200g
Carboxymethylstach sodium 50g
Hydroxypropyl methylcellulose 3.5g
Malic acid 100g
Micropowder silica gel 15g
Magnesium stearate 6.5g
Water 230g
95% ethanol 100g
Make 1000.
Preparation method is with embodiment 2.
Embodiment 6 changes filler, and replace lactose with starch, and malic acid is replaced to citric acid, the made dispersible tablet there was no significant difference of dispersible tablet and embodiment 3, dispersibility and dissolution are all better.
Embodiment 7
Tenoxicam 20g
Icing Sugar 250g
Crospolyvinylpyrrolidone 150g
Carboxymethylstach sodium 150g
Hydroxypropyl methylcellulose 3.5g
Citric acid 100g
Micropowder silica gel 15g
Magnesium stearate 7.5g
Water 229g
95% ethanol 100g
Make 1000.
Preparation method is with implementing 2.
Embodiment 7 changes filler, replaces lactose with Icing Sugar, all the other with embodiment 3 together, the made dispersible tablet there was no significant difference of dispersible tablet and embodiment 3, dispersibility and dissolution are all better.
Embodiment 8
Tenoxicam 20g
Starch 300g
Crospolyvinylpyrrolidone 100g
Carboxymethylstach sodium 150g
Hydroxypropyl methylcellulose 3.5g
Maleic acid 100g
Micropowder silica gel 15g
Magnesium stearate 7.5g
Water 229g
95% ethanol 100g
Make 1000.
Preparation method is with embodiment 7.
The made dispersible tablet smooth in appearance of embodiment 8, dissolution are good, and dispersibility is slightly poorer than adopting the dispersible tablet of citric acid, but adopts the dispersible tablet of oxalic acid to get well.
Embodiment 9
Tenoxicam 10g
Lactose 300g
Crospolyvinylpyrrolidone 100g
Carboxymethylstach sodium 200g
Hydroxypropyl methylcellulose 3.5g
Citric acid 100g
Micropowder silica gel 25g
Magnesium stearate 7.5g
Water 175
95% ethanol 114g
Make 1000.
Preparation method is with embodiment 2.
The made dispersible tablet smooth in appearance of embodiment 9, dissolution are good.
Biological test
(1) table 1 is the dissolution comparative result of tenoxicam dispersible tablet and tenoxicam ordinary tablet (embodiment 1 gained dispersible tablet).
With reference to dissolution method (2010 editions two annex XC bis-methods of Chinese Pharmacopoeia).
The comparison of ordinary tablet cumulative percentage dissolution is sold in table 1 tenoxicam dispersible tablet and market
As can be seen from Table 1, the dissolution in vitro of tenoxicam dispersible tablet in 10-30min is obviously better than ordinary tablet.
(2) tenoxicam dispersible tablet assay
Measure with reference to high-efficient liquid phase technique (two annex VD of Chinese Pharmacopoeia version in 2010).
Table 2 tenoxicam dispersible tablet assay
| Batch | Tenoxicam dispersible tablet content (%) |
| Batch 1 | 100.31 |
| Batches 2 | 100.29 |
| Batches 3 | 100.40 |
As can be seen from Table 2, the content of the tenoxicam dispersible tablet requirement that conforms with the regulations.
(3) the quality stability comparison of tenoxicam dispersible tablet
Tenoxicam dispersible tablet accelerated test: the tenoxicam dispersible tablet of blister package is put under the condition of 40 DEG C ± 2 DEG C of temperature, relative humidity 75% ± 5% and placed six months, outcome quality is stable, and indices is as shown in table 3.
Six months accelerated test testing results of table 3 tenoxicam dispersible tablet
| Inspection batch | Outward appearance | Disintegration | Dispersing uniformity | Dissolution % | Content % |
| Batch 1 | Faint yellow smooth | 39 | Conform with the regulations | 100.32 | 100.16 |
| Batches 2 | Faint yellow smooth | 39 | Conform with the regulations | 100.14 | 100.08 |
| Batches 3 | Faint yellow smooth | 40 | Conform with the regulations | 100.21 | 100.13 |
Claims (10)
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101619070A (en) * | 2009-07-24 | 2010-01-06 | 浙江大学 | Preparation method of tenoxicam |
| CN102266300A (en) * | 2011-07-14 | 2011-12-07 | 广东药学院 | Gefitinib dispersible tablet and preparation method and application thereof |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101619070A (en) * | 2009-07-24 | 2010-01-06 | 浙江大学 | Preparation method of tenoxicam |
| CN102266300A (en) * | 2011-07-14 | 2011-12-07 | 广东药学院 | Gefitinib dispersible tablet and preparation method and application thereof |
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